People living with chronic kidney disease (CKD) are at higher risk of a number of outcomes, including myocardial infarction, acute kidney injury, and death. Risk factors for these outcomes, such as infections and other co-morbidities, have been studied in this population; however, one potential risk factor that has still not been studied is bereavement. The period following the death of a loved one has been shown to be associated with a substantially higher risk of sudden-onset illness and death, particularly in men and those at high cardiovascular risk at a younger age. There are currently no data on how those living with kidney disease are affected by this type of stress. We will study the risk of acute cardiovascular events, acute kidney injury, and death in a cohort of people with CKD experiencing bereavement compared to CKD patients not experiencing bereavement. Results of this analysis could inform future studies examining interventions to reduce a possible increased risk of complications in people with chronic kidney disease experiencing acute periods of stress, particularly during bereavement.
Bereavement is a known risk factor for a variety of poor cardiovascular outcomes and death. To our knowledge, there are no studies which have assessed the impact partner bereavement may have on cardiovascular and kidney outcomes specifically in patients with pre-existing chronic kidney disease (CKD). This study will be designed as a matched historical cohort study to investigate a possible association between partner bereavement and an increased risk of cardiovascular events, acute kidney injury, and death in people with CKD. This study will use primary care data from the Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics (HES) and Office for National Statistics (ONS) data to determine exposure, outcome, and confounder statuses in our study population. Partners will be identified in the CPRD using the family number and restricted to those with CKD, whilst maintaining de-identification of individual patient data. The exposure of interest is partner bereavement in patients with CKD. Each bereaved (exposed) individual will then be matched with up to 10 other people with CKD based on age, sex, and general practice. Matched unexposed patients must be alive at the exposed person's index date of bereavement but have never experienced partner bereavement before the index date. Time-to-event analyses (either Poisson or Cox models, depending on the shape of the relative hazards over time) will be used to investigate crude and adjusted associations of bereavement with CVD outcomes, AKI, and death. Crude and adjusted hazard ratios and 95% confidence intervals will be used to measure any possible associations between bereavement and adverse outcomes in the study population.
Outcomes (ICD-10 code):
First cardiovascular event after index date (myocardial infarction (I21), acute heart failure (I50), and stroke (I60, I61, I63, I64))
First acute kidney injury after index date (N17)
Death
Outcomes will derive from International Classification of Diseases (ICD) 10th revision codes recorded in the Hospital Episode Statistics (HES) dataset. We will identify dates of death using Office of National Statistics (ONS) data for those who had linkage to ONS and CPRD derived dates of death for those without linkage to ONS. Preliminary code lists for the outcomes are provided in the appendix. All outcomes will be identified in the cohort following the index date for both the exposed and unexposed groups, with each participant capable of contributing more than one outcome before censorship. For example, a participant may experience acute kidney injury, and then go on to experience stroke one month later. This participant would add to the event count of both outcomes in the analysis. We will only be considering the first outcome event after the index date; we will not be investigating repeat events of the same outcome during follow-up. Prevalent cardiovascular and kidney disease will be adjusted for in the adjusted regression models (see section N).
Each participant will be followed until one of the following: death, transfer out of the general practice (including for either member of the couple in the non-bereaved group), or the end of the observation period available (currently 31 July 2018).
Dorothea Nitsch - Chief Investigator - London School of Hygiene & Tropical Medicine ( LSHTM )
Patrick Bidulka - Corresponding Applicant - London School of Hygiene & Tropical Medicine ( LSHTM )
Christian Christiansen - Collaborator - Aarhus University Hospital
Liam Smeeth - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Sigrún Alba Jóhannesdóttir Schmidt - Collaborator - Aarhus University Hospital
Sinead Langan - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Soren Vestergaard - Collaborator - Aarhus University Hospital
Yochai Schonmann - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Yun "Angel" Wong - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation